Novel dichloromaleic acid diamide derivatives and their use as fungicides

ABSTRACT

Dichloromaleic acid diamides of the formula   &lt;IMAGE&gt;   in which R represents an optionally substituted aliphatic radical with up to 8 carbon atoms, a cycloalkyl radical with 3 to 6 carbon atoms or a substituted phenyl radical, which possess fungicidal properties, are produced by reacting a dichloromaleic halide of the formula   &lt;IMAGE&gt; in which X is halogen, with an amine of the formula H2N-R in a diluent and in the presence of an acid-binding agent.

The present invention relates to and has for its objects and provisionof particular new dichloromaleic acid diamides which possess fungicidalproperties, active compositions in the form of mixtures of suchcompounds with solid and liquid dispersible carrier vehicles, andmethods for producing such compounds and for using such compounds in anew way especially for combating pests, e.g. fungi, with other andfurther objects becoming apparent from a study of the withinspecification and accompanying examples.

It has already been disclosed thatN-(p-fluorophenyl)-2,3-dichloromaleimide has a very good action againstcitrus scab (see, for example, DT-OS (German Published Specification)No. 2,156,967 and U.S. Pat. No. 3,734,927). However, the spectrum ofaction of the compound mentioned is not completely satisfactory when lowamounts are applied. Furthermore, zincethylene-1,2-bis-dithiocarbamidate has been generally known for a longtime as a standard preparation with a fungicidal action (R. Wegler,"Chemie der Pflanzenschutz- and Schadlingsbekampfungsmittel" ("Chemistryof plant protection agents and agents for combating pests"),Springer-Verlag, Berlin/Heidelberg/New York (1970), volume 2, page 65).

Moreover, it has been known for a relatively long time that when anilineis acylated with dichloromaleic acid dichloride, a product mixture isformed (see, in this context, J. prakt. Chemie 130, 255 (1931)). Eventhough, as has also become known recently, the dichloromaleic aciddichloride exists exclusively in the lactoidal (cyclic) form astetrachloro-5H-furan-2-one, reactions of lactoidal acid chlorides ofdicarboxylic acids with nucleophilic reactants can in principle lead toproducts which contain an intact lactoidal ring (Chem. Ber. 104, 3,378(1971)), or can give open-chain derivatives, the ring being opened(Chem. Ber. 109, 1,163 (1976)). Accordingly, in the literature (J.prakt. Chem. 130, 255 (1931)), a product mixture is in each casedescribed when aniline is acylated with dichloromaleic acid dichloride,and in particular a yellow product with a melting point of 170° C. and awhite product with a melting point of 193° C., both products having thesame empirical formula C₁₆ H₁₂ Cl₂ N₂ O₂. Formation of solely the whiteproduct (melting point 193° C.), which is described as symmetricdichloromaleic acid bisphenylamide, was only possible if thedichloromaleic acid dichloride had first been subjected to a treatmentwith aluminum chloride, which was explained as conversion of thelactoidal form into the open-chain symmetric form.

No biological actions have hitherto been disclosed for theabove-mentioned, previously described dichloromaleic acidbis-phenylamide (J. prakt. Chem. 130, 255 (1931).

The present invention now provides, as new compounds, the dichloromaleicacid diamide derivatives of the general formula ##STR3## in which Rrepresents an optionally substituted aliphatic radical with up to 8carbon atoms, a cycloalkyl radical with 3 to 6 carbon atoms or asubstituted phenyl radical.

Preferably, R represents a straight-chain or branched, saturated orunsaturated aliphaic radical with up to 6 carbon atoms, which canoptionally carry one or more substituents selected from halogen atoms,cyano, C₁ -C₄ alkoxy, C₁ -C₄ alkylthio, phenyl, phenoxy, a heterocyclicgroup which contains 5 or 6 ring members, which can be saturated orunsaturated and which contains one or more hetero-atoms selected fromoxygen atoms, sulphur atoms and nitrogen atoms (examples which may bementioned are the furyl group, the pyranyl group (derivatives of pyrane)and hydrogenated and partially hydrogenated derivatives thereof), andthe amino group, each hydrogen atom of which optionally can be replacedby alkyl with up to 4 carbon atoms or by phenyl; or represents acycloalkyl group with 5 or 6 carbon atoms; or represents phenyl that iscarrying one or more substituents each selected independently fromalkyl, alkenyl, alkynyl, alkoxy and alkylthio with up to 3 carbon atomsin each case, phenyl, phenoxy, halogen, nitro, cyano, halogenomethyl(for example trifluoromethyl), halogenoethyl, trifluoromethoxy,trifluoromethylthio, thiocyanato, carboxyl groups and alkoxycarbonylgroups with up to 4 carbon atoms in the alkyl part, and the acetylaminogroup.

Surprisingly, the dichloromaleic acid diamide derivatives of the formula(I) according to the invention exhibit a considerably more powerfulfungicidal action than the compounds known from the state of the art.The substances according to the invention thus represent an enrichmentof the art.

The invention also provides a process for the production of adichloromaleic acid diamide derivative of the formula (I), in which adichloromaleic acid halide of the general formula ##STR4## in which Xrepresents halogen, preferably chlorine, is reacted with an amine of thegeneral formula

    H.sub.2 N--R                                               (III),

in which

R has the meaning stated above,

in a diluent and in the presence of an acid-binding agent.

Finally, as has also been found, a course of reaction leading solely tothe open-chain symmetric compounds of the general formula (I) (even whencompounds of the lactoidal type IIa are used as starting materials), caneasily be effected by initially introducing into the reaction vessel theamine of the formula (III) to be acylated and then adding thedichloromaleic acid halide (formula IIa or IIb).

Furthermore, it is surprising that the formation of the single productsof the formula (I) is achieved in a simple manner by the additionsequence according to the invention. The omission of the treatment ofthe dichloromaleic acid halide with aluminum chloride or another Lewisacid, which was necessary according to previous knowledge, denotes asimplification of the art.

If tetrachloro-5H-furan-2-one ("dichloromaleic acid dichloride") andethylamine are used as starting materials, the course of the reactioncan be represented by the equation which follows: ##STR5##

The dichloromaleic acid halides of the formula (II) are known and can beprepared by processes which are generally known, for example byhalogenating dichloromaleic acid anhydride, for example either by usingphosphorus pentachloride, phosgene or thionylchloride, or by usinghalogen, such as chlorine, in the presence of a catalyst, such as, forexample, an iron salt.

The amines of the formula (III) are known compounds which are obtainablein a generally known manner and are customary in organic chemicallaboratories. Thus, for example, [tetrahydropyran-2-yl]-methylamine,also called 2-aminomethyl-tetrahydropyrane, is obtained by hydrogenating2-cyano-tetrahydropyrane, for example with lithium alanate or withhydrogen under pressure (see Beilstein 18, E 3/4, page 7,045). On theother hand, 2-aminomethyl-3,4-dihydropyrane can be prepared byhydrogenating 2-formyl-3,4-dihydropyrane under pressure, in the presenceof ammonia.

The amines can, of course, also be used in the form of theiracid-addition products, for example in the form of their hydrochloridesor hydrobromides, or in the form of adducts with organic acids, fumaricacid being mentioned as an example here.

Diluents which can be used for the reaction according to the inventionare all the customary polar solvents. Water is preferably used, and alsoalcohols, for example methanol, ethanol or propanol, as well as ketones,such as acetone. Moreover, mixtures of different solvents can also beused, for example mixtures consisting of water and a water-misciblesolvent.

Any of the customary acid-binding agents (bases) can be used asauxiliaries, especially inorganic acid-binding agents, such as alkalimetal hydroxides and alkali metal carbonates, for example sodiumhydroxide and potassium carbonate. If the reaction is carried out in anorganic solvent, a tertiary amine is preferably used, for exampletriethylamine or pyridine.

Preferably, the amine of the formula (III) to be used as the startingmaterial can also be used in excess and can thus simultaneously functionas a reactant and as the acid-binding agent.

The reaction temperatures can be varied within a substantial range. Ingeneral, the reaction is carried out at about -5° to +150° C.,preferably about +10° to 50° C.

In carrying out the process according to the invention, 2 moles of theamine of the formula (III) and at least 2 moles of an acid-binding agentare preferably employed per mole of dichloromaleic acid dihalide of theformula (IIa) or (IIb), it also being possible, as already mentioned, touse the amine of the formula (III) in excess instead of a separateacid-binding agent; in the latter case, at least 4 moles of amine arethen required per mole of dichloromaleic acid dihalide. The mixture isworked up in the usual manner, for example by a procedure in which theend product, which has precipitated from water, is filtered off anddried.

The active compounds according to the invention exhibit a powerfulfungitoxic action. They do not damage crop plants in the concentrationsrequired for combating fungi. For these reasons, they are suitable foruse as plant protection agents for combating fungi. Fungitoxic agentsare employed in plant protection for combating Plasmodiophoromycetes,Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetesand Deuteromycetes.

The active compounds according to the invention have a broad spectrum ofaction and can be used against parasitic fungi which attack above-groundparts of plants or which attack the plants through the soil, as well asagainst seed-borne pathogens.

Thus they exhibit a particularly good activity against the causativeorganism of blight and brown rot of tomatoes (Phytophthora infestans)and the fungus Pyricularia oryzae, which causes a disease in rice.

In the cultivation of cereals, the active compounds have a good activityagainst cereal rust (Puccinia recondita), bunt of wheat (Tilletiacaries) and stripe disease of barley (Helminthosporium gramineum).

As plant protection agents, the compounds according to the invention canbe used for the treatment of soil, for the treatment of seed and for thetreatment of above-ground parts of plants.

The active compounds can be converted into the customary formulations,such as solutions, emulsions, wettable powders, suspensions, powders,dusting agents, foams, pastes, soluble powders, granules, aerosols,suspension-emulsion concentrates, seed-treatment powders, natural andsynthetic materials impregnated with active compound, very fine capsulesin polymeric substances, coating compositions for use on seed, andformulations used with burning equipment, such as fumigating cartridges,fumigating cans and fumigating coils, as well as ULV cold mist and warmmist formulations.

These formulations may be produced in known manner, for example bymixing the active compounds with extenders, that is to say liquid orliquefied gaseous or solid diluents or carriers, optionally with the useof surface-active agents, that is to say emulsifying agents and/ordispersing agents and/or foam-forming agents. In the case of the use ofwater as an extender, organic solvents can, for example, also be used asauxiliary solvents.

As liquid solvents diluents or carriers, especially solvents, there aresuitable in the main, aromatic hydrocarbons, such as xylene, toluene oralkyl naphthalenes, chlorinated aromatic or chlorinated aliphatichydrocarbons, such as chlorobenzenes, chloroethylenes or methylenechloride, aliphatic or alicyclic hydrocarbons, such as cyclohexane orparaffins, for example mineral oil fractions, alcohols, such as butanolor glycol as well as their ethers and esters, ketones, such as acetone,methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, orstrongly polar solvents, such as dimethylformamide anddimethylsulphoxide, as well as water.

By liquefied gaseous diluents or carriers are meant liquids which wouldbe gaseous at normal temperature and under normal pressure, for exampleaerosol propellants, such as halogenated hydrocarbons as well as butane,propane, nitrogen and carbon dioxide.

As solid carriers there may be used ground natural minerals, such askaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite ordiatomaceous earth, and ground synthetic minerals, such ashighly-dispersed silicic acid, alumina and silicates. As solid carriersfor granules there may be used crushed and fractionated natural rockssuch as calcite, marble, pumice, sepiolite and dolomite, as well assynthetic granules of inorganic and organic meals, and granules oforganic material such as sawdust, coconut shells, corn cobs and tobaccostalks.

As emulsifying and/or foam-forming agents there may be used non-ionicand anionic emulsifiers, such as polyoxyethylene-fatty acids esters,polyoxyethylene-fatty alcohol ethers, for example alkylaryl polyglycolethers, alkyl sulphonates, alkyl sulphates, aryl, sulphonates as well asalbumin hydrolysis products. Dispersing agents include, for example,lignin sulphite waste liquors and methylcellulose.

Adhesives such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latices, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, can be used in theformulations.

It is possible to use colorants such as inorganic pigments, for exampleiron oxide, titanium oxide and Prussian Blue, and organic dyestuffs,such as alizarin dyestuffs, azo dyestuffs or metal phthalocyaninedyestuffs, and trace nutrients, such as salts of iron, manganese, boron,copper, cobalt, molybdenum and zinc.

The formulations in general contain from 0.1 to 95 percent by weight ofactive compound, preferably from 0.5 to 90 percent by weight.

The active compounds according to the invention can be present in theformulations as a mixture with other active compounds, such asfungicides, insecticides, acaricides, nematicides, herbicides, birdrepellents, growth factors, plant nutrients and agents for improvingsoil structure.

The active compounds can be used as such, as their formulations or asthe use forms prepared therefrom by further dilution, such asready-to-use solutions, emulsions, suspensions, powders, pastes andgranules. They may be used in the customary manner, for example bywatering, spraying, atomizing, dusting, scattering, dry dressing, moistdressing, wet dressing, slurry dressing or encrusting.

Especially when used as leaf fungicides and leaf bactericides, theactive compound concentrations in the use forms can be varied within asubstantial range. They are, in general, from 0.5 to 0.0005% by weight,preferably from 0.2 to 0.001%.

In the treatment of seed, amounts of active compound of 0.01 to 50 g,especially 0.5 to 5 g, are generally employed per kilogram of seed.

For the treatment of soil, amounts of active compound of 1 to 1,000 g,preferably 10 to 200 g, are generally employed per cubic meter of soil.

In addition to the fungicidal action, the compounds according to theinvention also exhibit, when applied in the appropriate amounts andconcentrations, an action as plant growth regulators.

The present invention also provides a fungicidal composition containingas active ingredient a compound of the present invention in admixturewith a solid or liquefied gaseous diluent or carrier or in admixturewith a liquid diluent or carrier containing a surface-active agent.

The present invention also provides a method of combating fungi whichcomprises applying to the fungi, or to a habitat thereof, a compound ofthe present invention alone or in the form of a composition containingas active ingredient a compound of the present invention in admixturewith a diluent or carrier.

The present invention further provides crops protected from damage byfungi by being grown in areas in which immediately prior to and/orduring the time of the growing a compound of the present invention wasapplied alone or in admixture with a diluent or carrier.

It will be seen that the usual methods of providing a harvested crop maybe improved by the present invention.

The preparation of the novel compounds is shown in the followingillustrative examples:

EXAMPLE 1 ##STR6##

10.0 g (45.1 mmoles) of tetrachloro-5-furan-2-one ("dichloromaleic aciddichloride") were introduced slowly into 40 ml of a 25% strengthethylamine solution at room temperature, while stirring vigorously. Theproduct which precipitated was filtered off and dried. 8.7 g ofdichloromaleic acid bis-ethylamide of melting point 154°-155° C. whereobtained. The yield was 81% of theory.

EXAMPLE 2 ##STR7##

22.2 g (0.1 mol) of dichloromaleic acid dichloride were introducedslowly into a mixture of 20.2 g (0.2 mol) of triethylamine and 19.4 g(0.2 mol) of furfurylamine in 200 ml of acetone at room temperature,while stirring vigorously. The reaction mixture was poured into 100 mlof water and the product which precipitated was filtered off and dried.29.0 g of dichloromaleic acid bis-furfurylamide of melting point 149° C.were obtained. The yield was 85% of theory.

EXAMPLE 3 ##STR8##

160 g of 10% strength sodium hydroxide solution were added to 40.1 g(0.4 mol) of 2-chloroethylamine hydrochloride, dissolved in 150 ml ofwater, and 22.2 g (0.1 mol) of dichloromaleic acid dichloride were thenintroduced slowly at room temperature. The product which precipitatedwas filtered off and dried. 19.7 g of dichloromaleic acidbis-(2-chloroethyl)-amide of melting point 107°-110° C. were obtained,that is to say 64% of theory.

The compounds of the general formula ##STR9## in which R has themeanings given below were prepared analogously to the above examples.

    ______________________________________                                        Compound                     Melting                                          No.       R                  point (°C.)                               ______________________________________                                        4         CH.sub.3           162-163                                          5         C.sub.3 H.sub.7 (n)                                                                              135-137                                          6         C.sub.4 H.sub.9 (n)                                                                              130-132                                          7         C.sub.4 H.sub.9 (i)                                                                              166-167                                          8         CH.sub.2CHCH.sub.2 127                                              9         CH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.3                                                              83-85                                           10                                                                                       ##STR10##         113-116                                          11                                                                                       ##STR11##         139-140                                          12                                                                                       ##STR12##         133-134                                          13                                                                                       ##STR13##         187-190                                          14                                                                                       ##STR14##         185                                              15                                                                                       ##STR15##         147-149                                          16                                                                                       ##STR16##         138-140                                          17                                                                                       ##STR17##         146                                              18                                                                                       ##STR18##         178                                              19        CH.sub.2C(CH.sub.3)CH.sub. 2                                                                     124-125                                          20        CH.sub.2CCH        124-126                                          ______________________________________                                    

The fungicidal activity of the compounds of this invention isillustrated by the following examples, wherein the compounds accordingto the present invention are each identified by the number (given inbrackets) from the preparative examples hereinabove.

EXAMPLE 4

Mycelium growth test

Nutrient medium used;

20 parts by weight of agar-agar

200 parts by weight of potato decoction

5 parts by weight of malt

15 parts by weight of dextrose

5 parts by weigt of peptone

2 parts by weight of disodium hydrogen phosphate

0.3 part by weight of calcium nitrate

Composition of the solvent mixture:

0.19 part by weight of dimethylformamide

0.01 part by weight of emulsifier (alkylaryl polyglycol ether)

1.80 parts by weight of water

Ratio of solvent mixture to nutrient medium:

2 parts by weight of solvent mixture

100 parts by weight of agar nutrient medium

The amount of active compound required for the desired active compoundconcentration in the nutrient medium was mixed with the stated amount ofsolvent mixture. The concentrate was thoroughly mixed, in the statedproportion, with the liquid nutrient medium (which has been cooled to 42deg. C.) and was then poured into Petri dishes of 9 cm diameter. Controlplates to which the preparation had not been added were also set up.

When the nutrient medium had cooled and solidified, the plates wereinoculated with the species of fungi indicated below and incubated atabout 21° C.

Evaluation was carried out after 4-10 days, dependent upon the speed ofgrowth of the organisms. When evaluation was carried out the radialgrowth of the organism on the treatment nutrient media was compared withthe growth on the control nutrient medium.

Evaluation of the test showed that, for example, the compounds (1), (6),(7), (15), (14), (2), (3), (8) and (11) had an action against thespecies of fungi Sclerotinia sclerotiorum, Fusarium nivale,Colletotrichum coffeanum, Rhizoctonia solani, Verticillium alboatrum,Pyricularia oryzea, Helminthosporium gramineum, Mycosphaerella musicola,Phytophthora cactorum and Pellicularia sasakii superior to that of thecompounds known from the prior art.

EXAMPLE 5

Pyricularia test/liquid preparation of active compound.

Solvent: 11.75 parts by weight of acetone.

Dispersing agent: 0.75 part by weight of alkylaryl polyglycol ether.

Water: 987.50 parts by weight.

The amount of active compound required for the desired concentration ofactive compound in the watering liquid was mixed with the stated amountof the solvent and dispersing agent and the concentrate was diluted withthe stated amount of water.

Rice plants about 14 days old were sprayed with the spray liquid untildripping wet. The plants remained in a greenhouse at temperatures of 22°to 24° C. and a relative atmospheric humidity of about 70% until theywere dry. They were then inoculated with an aqueous suspension of100,000 to 200,000 spores/ml of Pyricularia oryzae and set up in achamber at 24° to 26° C. and 100% relative atmospheric humidity.

5 days after the inoculation, the infection of all the leaves present atthe time of inoculation was determined as a percentage of the untreated,but also inoculated, control plants.

The evaluation showed that, for example, the compounds (1), (6), (7),(15), (14), (18), (2), (3), (8) and (11) had a superior action to thatof the compounds known from the prior art.

EXAMPLE 6

Phytophthora test (tomato)/protective.

Solvent: 4.7 parts by weight of acetone.

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether.

Water: 95 parts by weight.

The amount of the active compound required for the desired concentrationof the active compound in the spray liquid was mixed with the statedamount of solvent and the concentrate was diluted with the stated amountof water which contained the stated additions.

Young tomato plants with 2 to 4 foliage leaves were sprayed with thespray liquid until dripping wet. The plants remained in a greenhouse for24 hours at 20 deg. C. and at a relative atmospheric humidity of 70%.The tomato plants were then inoculated with an aqueous spore suspensionof Phytophthora infestans. The plants were brought into a moist chamberwith an atmospheric humidity of 100% and a temperature of 18°-20 deg. C.

After 5 days the infection of the tomato plants was determined.Evaluation of the test showed that, for example, the compounds (6),(15), (2), (10), (8), (16), (17) and (11) had a superior action to thatof the compounds known from the prior art.

It will be appreciated that the instant specification and examples areset forth by way of illustration and not limitation, and that variousmodifications and changes may be made without departing from the spiritand scope of the present invention.

What is claimed is:
 1. A dichloromaleic acid diamide selected from thegroup consisting ofdichloromaleic acid bis-(2-chloroethyl)-amide,dichloromaleic acid bis-n-butylamide, dichloromaleic acid bis-allylamideand dichloromaleic acid bis-3-trifluoromethylanilide.
 2. A compoundaccording to claim 1, wherein such compound is dichloromaleic acidbis-(2-chloroethyl)-amide of the formula ##STR19##
 3. A compoundaccording to claim 1, wherein such compound is dichloromaleic acidbis-n-butylamide of the formula ##STR20##
 4. A compound according toclaim 1, wherein such compound is dichloromaleic acid bis-allylamide ofthe formula ##STR21##
 5. A compound according to claim 1, wherein suchformula is dichloromaleic acid bis-3-trifluoromethylanilide of theformula ##STR22##
 6. A fungicidal composition containing a diluent inadmixture with a fungicidally effective amount of a dichloromaleic aciddiamide of the formula ##STR23## in which R is an aliphatic radical withup to 6 carbon atoms which can optionally carry one or more substituentsselected from halogen atoms, cyano, C₁ -C₄ alkoxy, C₁ -C₄ alkylthio,phenyl, phenoxy, amino, C₁₋₄ -alkylamino or phenylamino; a cycloalkylgroup with 5 or 6 carbon atoms; or phenyl carrying at least onesubstituent selected independently from alkyl, alkenyl, alkynyl, alkoxyand alkylthio each with up to 3 carbon atoms, phenyl, phenoxy, halogen,nitro, cyano, halogenomethyl, halogenoethyl, trifluoromethoxy,trifluoromethylthio, thiocyanato, carboxyl, alkoxycarbonyl with up to 4carbon atoms in the alkyl part, and acetylamino.
 7. A method ofcombating fungi which comprises applying to the fungi, or to a habitatthereof, a fungicidally effective amount of a dichloromaleic aciddiamide of the formula ##STR24## in which R is an aliphatic radical withup to 6 carbon atoms which can optionally carry one or more substituentsselected from halogen atoms, cyano, C₁ -C₄ alkoxy, C₁ -C₄ alkylthio,phenyl, phenoxy, amino, C₁₋₄ -alkylamino or phenylamino; a cycloalkylgroup with 5 or 6 carbon atoms; or phenyl carrying at least onesubstituent selected independently from alkyl, alkenyl, alkynyl, alkoxyand alkylthio each with up to 3 carbon atoms, phenyl, phenoxy, halogen,nitro, cyano, halogenomethyl, halogenoethyl, trifluoromethoxy,trifluoromethylthio, thiocyanato, carboxyl, alkoxycarbonyl with up to 4carbon atoms in the alkyl part, and acetylamino.
 8. A method accordingto claim 7, in which the compound is dichloromaleic acidbis-(2-chloroethyl)-amide, dichloromaleic acid bis-n-butylamide,dichloromaleic acid bis-allylamide or dichloromaleic acidbis-3-trifluoromethylanilide.